43 research outputs found

    Stressing the Ubiquitin-Proteasome System without 20S Proteolytic Inhibition Selectively Kills Cervical Cancer Cells

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    Cervical cancer cells exhibit an increased requirement for ubiquitin-dependent protein degradation associated with an elevated metabolic turnover rate, and for specific signaling pathways, notably HPV E6-targeted degradation of p53 and PDZ proteins. Natural compounds with antioxidant properties including flavonoids and triterpenoids hold promise as anticancer agents by interfering with ubiquitin-dependent protein degradation. An increasing body of evidence indicates that their α-β unsaturated carbonyl system is the molecular determinant for inhibition of ubiquitin-mediated protein degradation up-stream of the catalytic sites of the 20S proteasome. Herein we report the identification and characterization of a new class of chalcone-based, potent and cell permeable chemical inhibitors of ubiquitin-dependent protein degradation, and a lead compound RAMB1. RAMB1 inhibits ubiquitin-dependent protein degradation without compromising the catalytic activities of the 20S proteasome, a mechanism distinct from that of Bortezomib. Treatment of cervical cancer cells with RAMB1 triggers unfolded protein responses, including aggresome formation and Hsp90 stabilization, and increases p53 steady state levels. RAMB1 treatment results in activation of lysosomal-dependent degradation pathways as a mechanism to compensate for increasing levels of poly-ubiquitin enriched toxic aggregates. Importantly, RAMB1 synergistically triggers cell death of cervical cancer cells when combined with the lysosome inhibitor Chloroquine

    Contribution of PEPFAR-Supported HIV and TB Molecular Diagnostic Networks to COVID-19 Testing Preparedness in 16 Countries.

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    The US President's Emergency Plan for AIDS Relief (PEPFAR) supports molecular HIV and tuberculosis diagnostic networks and information management systems in low- and middle-income countries. We describe how national programs leveraged these PEPFAR-supported laboratory resources for SARS-CoV-2 testing during the COVID-19 pandemic. We sent a spreadsheet template consisting of 46 indicators for assessing the use of PEPFAR-supported diagnostic networks for COVID-19 pandemic response activities during April 1, 2020, to March 31, 2021, to 27 PEPFAR-supported countries or regions. A total of 109 PEPFAR-supported centralized HIV viral load and early infant diagnosis laboratories and 138 decentralized HIV and TB sites reported performing SARS-CoV-2 testing in 16 countries. Together, these sites contributed to >3.4 million SARS-CoV-2 tests during the 1-year period. Our findings illustrate that PEPFAR-supported diagnostic networks provided a wide range of resources to respond to emergency COVID-19 diagnostic testing in 16 low- and middle-income countries

    Efficacy of Crestar (Progesterone analogue) and Prosolvin (Prostaglandin analogue) in heat synchronization of indigenous smallholder dairy and commercial beef cows

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    Efficient breeding program for livestock improvement cannot be designed in the absence of prior knowledge of heat synchronization coupled with artificial insemination. Comparison of a prostaglandin (Prosolvin) and a progesterone analogue (Crestar) in heat synchronization in smallholder dairy and commercial beef cows was done in Mutoko, Beatrice and Marondera. The research aimed at establishing the estrus response and conception rates of animals synchronized. A total of 106 cows of Mashona, Brahman and Tuli breeds in second and third parity were used in the study. All the cows were of body condition score three. Equal numbers of animals were treated with Prosolvin and Crestar in three districts, ear tagged and confined in the paddock. The stockmen were responsible for estrus detection. Insemination was done based on the AM-PM rule. Conception rates were determined after three months by rectal palpation. The data was subjected to Chi-Square Tests for association using Gen Stat Statistical Package (7.2 version). The Prosolvin treated cows had a higher estrus response of 85% while the Crestar treated animals had a lower mean estrus response of 67%. The parity, cow breed and enterprise had no significant effect on estrus response (P>0.05). Silent estrus was associated with Crestar treated cows significantly more (7%) than with Prosolvin treated cows (2%). The treatments for heat synchronization had no significant effect on conception rate (P>0.05). The parity, cow breed and breed of semen used for insemination had a significant effect on conception rate (P<0.05) with third parity, Tuli breed and Red Dane semen breed having the highest conception rate (54%, 54% and 58% respectively). The procedures of thawing frozen semen and the techniques of semen deposition through the cervix have to be properly followed to achieve high conception rates. Animals can also be inseminated twice to increase chances of conception. Keywords: Artificial Insemination, Brahman, conception rate, estrus, Mashona, Tul

    Mapping cassava food value chains in Tanzania's smallholder farming sector: the implications of intra-household gender dynamics.

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    Published online: 08 Jan 2018A gendered mapping of the structure and coordination (functioning) of traditional cassava value chains is important for marginalized groups such as women in rural development. In contrast to global high value chains, traditional food value chains and associated gender relations as well as power dynamics within households have received little attention. We conducted a cross sectional study in Kigoma, Mwanza, the coastal region, and Zanzibar Island in Tanzania. Data were collected through structured interviews conducted with 228 farmers, combined with key informant interviews, direct observations, repeated household visits, and literature review. The results of the study revealed that there are weak linkages within the cassava value chain, which is highly gendered. While production and processing nodes of the chain, which commenced from villages, were dominated by women and children, women were not well-integrated within high value nodes such as marketing in urban areas and cross-border trading, which were dominated by men. Transportation of cassava to highly lucrative markets was also dominated by men. Cassava processing was conducted at the household level as well as within small-scale cooperatives, with the major portion of this work being done by women. Supporting institutions were found to be involved in the supply of planting material, training, and the provision of processing equipment. In general, men played a prominent role in the control of resources, marketing, and income. In conclusion, the mapping of cassava value chains could help to identify avenues for understanding of poverty, enhancing food security, upgrading capacities, reducing gender inequality, and enhancing women's participation in marketing and income control in the cassava value chains

    Women's empowerment in traditional food value chains at the micro-level: evidence from cassava smallholder farming in Tanzania

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    Posted online: 9 June 2017; Accepted manuscriptEmpowering women improves household food productivity and security. We examined women’s empowerment within the cassava value chain according to the five domains of empowerment of the Women’s Empowerment in Agriculture Index, using data from 228 respondents in Tanzania. Disempowerment indices for women and men were 0.95 and 0.14, respectively. Women were disempowered in the production, leadership, and time domains. Women were empowered in the resources domain, which entailed joint ownership and decision making. Marital status and educational levels were significantly associated with women’s empowerment. Policies to improve women’s empowerment should focus on securing ownership of resources and access to credit
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